Cell–cell interaction modulates neuroectodermal specification of embryonic stem cells
| Autor: | Daniel Irimia, Biju Parekkadan, Mehmet Toner, Martin L. Yarmush, John B. Levine, Avrum Leeder, Gabriel M. Yarmush, Yevgeny Berdichevsky |
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| Rok vydání: | 2008 |
| Předmět: |
Central Nervous System
Cellular differentiation Green Fluorescent Proteins Embryonic Development Cell Communication Biology Cell fate determination Article Cell Line Mice Cell–cell interaction Ectoderm Cell Adhesion medicine Animals Cell Lineage Neural Cell Adhesion Molecules Embryonic Stem Cells SOXB1 Transcription Factors General Neuroscience High Mobility Group Proteins Gap Junctions Cell Differentiation Molecular biology Embryonic stem cell Coculture Techniques Cell biology DNA-Binding Proteins medicine.anatomical_structure Cell culture Connexin 43 Neural cell adhesion molecule Stem cell Germ cell Signal Transduction |
| Zdroj: | Neuroscience Letters. 438:190-195 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/j.neulet.2008.03.094 |
| Popis: | The controlled differentiation of embryonic stem (ES) cells is of utmost interest to their clinical, biotechnological, and basic science use. Many investigators have combinatorially assessed the role of specific soluble factors and extracellular matrices in guiding ES cell fate, yet the interaction between neighboring cells in these heterogeneous cultures has been poorly defined due to a lack of conventional tools to specifically uncouple these variables. Herein, we explored the role of cell-cell interactions during neuroectodermal specification of ES cells using a microfabricated cell pair array. We tracked differentiation events in situ, using an ES cell line expressing green fluorescent protein (GFP) under the regulation of the Sox1 gene promoter, an early marker of neuroectodermal germ cell commitment in the adult forebrain. We observed that a previously specified Sox1-GFP+ cell could induce the specification of an undifferentiated ES cell. This induction was modulated by the two cells being in contact and was dependent on the age of previously specified cell prior to coculture. A screen of candidate cell adhesion molecules revealed that the expression of connexin (Cx)-43 correlated with the age-dependent effect of cell contact in cell pair experiments. ES cells deficient in Cx-43 showed aberrant neuroectodermal specification and lineage commitment, highlighting the importance of gap junctional signaling in the development of this germ layer. Moreover, this study demonstrates the integration of microscale culture techniques to explore the biology of ES cells and gain insight into relevant developmental processes otherwise undefined due to bulk culture methods. |
| Databáze: | OpenAIRE |
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